Genomic profile helps to predict the clonal evolution and outcome of BCR-ABL-negative myeloproliferative neoplasms.

Classical BCR-ABL-negative myeloproliferative neoplasms (MPNs) are a clonal expansion of myeloid precursors caused by somatic stem cells. Although driver mutations were observed in most MPN patients, the potential clonal disorder remains unclear. We analyzed a total of 1004 newly diagnosed MPN patients and next-generation sequencing was performed on the genomic DNA. Primary myelofibrosis (PMF) patients carried the highest LDH level, splenomegaly, and the lowest hemoglobin content. Myeloproliferative Neoplasm, unclassifiable (MPN-U) patients had higher platelet count and frequency of thrombotic events. The top five most frequently mutations were JAK2, ASXL1, TET2, CALR, and DNMT3A. The JAK2 mutation burden was positively correlated with leukocyte counts in all subgroups. PMF patients tend to have more somatic mutations than other patients. Among triple-negative (TN) MPN patients, SH2B3 and SRSF2 were positively correlated, and the NPM1 mutation rate was significantly increased. As for survival, we found that patients with PMF, MPN10 symptoms, JAK2 wild-type, or TN mutation were positively associated with shorter overall survival. The U2AF1 mutation was an independent risk factor for death in MPN patients, and ZRSR2, NF1, and PPM1D mutations were found in patients who progress to AML or MDS. In addition, we created a prediction nomogram by using five variables, which enhanced the precision of estimating survival in MPN patients. Our data provide a novel perspective for the diagnosis, clonal evolution and prognosis of MPNs.